{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T01:51:48Z","timestamp":1775526708059,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to verify whether the expression of proteins related to the formation of invadopodia, MT1-MMP, cortactin, Tks-4 and Tks-5 is associated with the degree of tumor invasiveness of different types of unicystic ameloblastomas. An immunohistochemical study was performed on 29 unicystic ameloblastoma (UA) samples, 9 conventional ameloblastoma (CAM) samples and 9 dental follicle (DF) samples. The potential for tumor invasiveness was assessed based on the immunoexpression of the following invadopodia-forming proteins: MT1-MMP, cortactin, Tks-4 and Tks5. Mural unicystic ameloblastoma (MUA) showed higher MT1-MMP, cortactin, Tks-4, and Tks-5 immunoexpression than luminal and intra-luminal types. Conventional ameloblastoma exhibited lower MT1-MMP, cortactin, and Tks-5 expression compared to MUA. MUA\u2019s cystic capsule neoplastic cells had significantly higher MT1-MMP, cortactin, Tks-4, and Tks-5 expression than lumen cells. Dental follicles showed minimal expression. Neoplastic cells in the cystic capsule of mural unicystic ameloblastomas showed higher invadopodia-related protein expression than lumen and luminal\/intraluminal cells, suggesting that proximity to the bone region influences the aggressive behavior of mural unicystic ameloblastomas more compared to other subtypes.<\/jats:p>","DOI":"10.3390\/ijms26031267","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T04:36:51Z","timestamp":1738557411000},"page":"1267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of Protein Immunoexpression Associated with Tumor Proliferation and Invasion in Histological Subtypes of Unicystic and Conventional Ameloblastoma"],"prefix":"10.3390","volume":"26","author":[{"given":"Gabriela Cristina Avertano Rocha","family":"da Silveira","sequence":"first","affiliation":[{"name":"Laboratory of Pathological Anatomy and Immunohistochemistry, School of Dentistry, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8784-5473","authenticated-orcid":false,"given":"Rebeca Vieira","family":"Costa","sequence":"additional","affiliation":[{"name":"Laboratory of Pathological Anatomy and Immunohistochemistry, School of Dentistry, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia Let\u00edcia Magalh\u00e3es","family":"Lemos","sequence":"additional","affiliation":[{"name":"Laboratory of Pathological Anatomy and Immunohistochemistry, School of Dentistry, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia Taiane Lopes","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (UNICAMP), Piracicaba 13414-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Sueli da Silva","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Cell Culture Laboratory, School of Dentistry, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-8626","authenticated-orcid":false,"given":"Vanessa Morais","family":"Freitas","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvio Augusto Fernandes","family":"de Menezes","sequence":"additional","affiliation":[{"name":"Department of Periodontics, University Center of Par\u00e1, Bel\u00e9m 66060-232, PA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Carolina Uchoa","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Center for the Diagnosis of Diseases of the Mouth, School of Dentistry, Federal University of Pelotas, Pelotas 96010-610, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6066-869X","authenticated-orcid":false,"given":"Adriana","family":"Etges","sequence":"additional","affiliation":[{"name":"Center for the Diagnosis of Diseases of the Mouth, School of Dentistry, Federal University of Pelotas, Pelotas 96010-610, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabricio Passador","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, S\u00e3o Leopoldo Mandic Institute and Research Center, Campinas 13045-755, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera Cavalcanti","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, S\u00e3o Leopoldo Mandic Institute and Research Center, Campinas 13045-755, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9rgio de Melo","family":"Alves J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Pathological Anatomy and Immunohistochemistry, School of Dentistry, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-0356","authenticated-orcid":false,"given":"Ruy Gastaldoni","family":"Jaeger","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6914-6441","authenticated-orcid":false,"given":"Jo\u00e3o de Jesus Viana","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Laboratory of Pathological Anatomy and Immunohistochemistry, School of Dentistry, Federal University of Par\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","unstructured":"El-Naggar, A.K., Chan, J.K.C., Grandis, J.R., Takata, T., and Slootweg, P.J. (2017). WHO Classification of Head and Neck Tumours, IARC. [4th ed.]."},{"key":"ref_2","unstructured":"WHO Classification of Tumors Editorial Board (2024). Head and Neck Tumours, IARC Publications. [5th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.tcb.2017.03.003","article-title":"Tumor cell invadopodia: Invasive protrusions that orchestrate metastasis","volume":"27","author":"Eddy","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ejcb.2008.01.008","article-title":"A new role for cortactin in invadopodia: Regulation of protease secretion","volume":"87","author":"Clark","year":"2008","journal-title":"Eur. J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/febs.14123","article-title":"Invadosomes are coming: New insights into function and disease relevance","volume":"285","author":"Paterson","year":"2018","journal-title":"FEBS J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nrm3141","article-title":"The \u2018ins\u2019 and \u2018outs\u2019 of podosomes and invadopodia: Characteristics, formation and function","volume":"12","author":"Murphy","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s10555-008-9176-1","article-title":"Invadopodia: Specialized tumor cell structures for the focal degradation of the extracellular matrix","volume":"28","author":"Buccione","year":"2009","journal-title":"Cancer Metastasis Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.archoralbio.2011.08.019","article-title":"Invadopodia formation in oral squamous cell carcinoma: The role of epidermal growth factor receptor signaling","volume":"57","author":"Hwang","year":"2012","journal-title":"Arch. Oral Biol."},{"key":"ref_9","first-page":"1","article-title":"Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2\/3 complex","volume":"15","author":"Millard","year":"2004","journal-title":"Biochem. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.oooo.2016.06.004","article-title":"Keratocystic odontogenic tumor overexpresses invadopodia-related proteins, suggesting invadopodia formation","volume":"122","author":"Ribeiro","year":"2016","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1091\/mbc.e08-09-0949","article-title":"The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation","volume":"20","author":"Buschman","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78473","DOI":"10.18632\/oncotarget.12954","article-title":"The role of Tks adaptor proteins in invadopodia formation, growth and metastasis of melanoma","volume":"7","author":"Iizuka","year":"2016","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1042\/BST20110685","article-title":"Cell migration and invasion in human disease: The Tks adaptor proteins","volume":"40","author":"Courtneidge","year":"2012","journal-title":"Biochem. Soc. Trans."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.yexmp.2018.11.005","article-title":"TKS5-positive invadopodia-like structures in human tumor surgical specimens","volume":"106","author":"Chen","year":"2018","journal-title":"Exp. Mol. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1242\/jcs.193904","article-title":"The role and regulation of Rab40b-Tks5 complex during invadopodia formation and cancer cell invasion","volume":"129","author":"Jacob","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/jop.12417","article-title":"Invadopodia proteins, cortactin, N-WASP and WIP differentially promote local invasiveness in ameloblastoma","volume":"45","author":"Siar","year":"2016","journal-title":"J. Oral Pathol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1080\/21541248.2017.1405773","article-title":"Cortactin function in invadopodia","volume":"11","author":"Jeannot","year":"2020","journal-title":"Small GTPases"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"88232","DOI":"10.18632\/oncotarget.21088","article-title":"Cortactin in cancer cell migration and invasion","volume":"19","author":"Yin","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.cub.2011.06.065","article-title":"Cortactin controls cell motility and lamellipodial dynamics by regulating ECM secretion","volume":"21","author":"Sung","year":"2011","journal-title":"Curr. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1016\/j.yexcr.2009.06.012","article-title":"Tks5 recruits AFAP-110, p190RhoGAP, and cortactin for podosome formation","volume":"315","author":"Crimaldi","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1111\/j.1365-2559.2011.03995.x","article-title":"Invadopodia proteins, cortactin and membrane type I matrix metalloproteinase (MT1-MMP) are expressed in ameloblastoma","volume":"59","author":"Pinheiro","year":"2011","journal-title":"Histopathology"},{"key":"ref_22","first-page":"514","article-title":"Podoplanin promotes the invasion of oral squamous cell carcinoma in coordination with MT1-MMP and Rho GTPases","volume":"5","author":"Li","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.bpj.2017.11.3777","article-title":"MMP secretion rate and inter-invadopodia spacing collectively govern cancer invasiveness","volume":"114","author":"Kumar","year":"2018","journal-title":"Biophys. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1365-2559.2001.01138.x","article-title":"Two relatively distinct patterns of ameloblastoma: An anti-apoptotic proliferating site in the outer layer (periphery) and a pro-apoptotic differentiating site in the inner layer (center)","volume":"39","author":"Sandra","year":"2001","journal-title":"Histopathology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.anorl.2015.08.016","article-title":"Study of Ki67 and CD10 expression as predictive factors of recurrence of ameloblastoma","volume":"132","author":"Ahlem","year":"2015","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1601-0825.2006.01284.x","article-title":"Ameloblastomas: A regional Latin-American multicentric study","volume":"13","year":"2007","journal-title":"Oral Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/jemt.20761","article-title":"Role of MMP9 on invadopodia formation in cells from adenoid cystic carcinoma. Study by laser scanning confocal microscopy","volume":"73","author":"Nascimento","year":"2010","journal-title":"Microsc. Res. Tech."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13000-021-01090-7","article-title":"Key proteins of invadopodia are overexpressed in oral squamous cell carcinoma suggesting an important role of MT1-MMP in the tumoral progression","volume":"16","author":"Mitre","year":"2021","journal-title":"Diagn. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/s41467-024-45558-8","article-title":"Intercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding","volume":"15","author":"Wenzel","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tanaka, N., and Sakamoto, T. (2023). MT1-MMP as a key regulator of metastasis. Cells, 12.","DOI":"10.3390\/cells12172187"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kudlik, G., Tak\u00e1cs, T., Radnai, L., Kurilla, A., Szeder, B., Koprivanacz, K., Mer\u0151, B.L., Buday, L., and Vas, V. (2020). Advances in understanding TKS4 and TKS5: Molecular scaffolds regulating cellular processes from podosome and invadopodium formation to differentiation and tissue homeostasis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218117"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"273","DOI":"10.4161\/cam.28349","article-title":"Invadopodia in context","volume":"8","author":"Bergman","year":"2014","journal-title":"Cell Adhes. Migr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Iizuka, S., Leon, R.P., Gribbin, K.P., Zhang, Y., Navarro, J., Smith, R., Devlin, K., Wang, L.G., Gibbs, S.L., and Korkola, J. (2020). Crosstalk between invadopodia and the extracellular matrix. Eur. J. Cell Biol., 99.","DOI":"10.1101\/2020.02.26.966762"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1365-2559.2004.01902.x","article-title":"Local invasiveness of ameloblastoma: Role played by matrix metalloproteinases and proliferative activity","volume":"45","author":"Pinheiro","year":"2004","journal-title":"Histopathology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vieira Costa, R., Balbinot, K.M., da Silveira, G.C.A.R., Kataoka, M.S.D.S., de Menezes, S.A.F., Freitas, V.M., Vasconcelos, A.C.U., Etges, A., Martins Montalli, V.A., and Santos, F.P. (2024). Prognostic value of the expression and localization of cell proliferation and apoptosis markers in unicystic ameloblastomas. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-54132-7"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/cm.20361","article-title":"N-WASP and cortactin are involved in invadopodium-dependent chemotaxis to EGF in breast tumor cells","volume":"66","author":"Desmarais","year":"2009","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1093\/carcin\/23.6.1065","article-title":"Membrane-type matrix metalloproteinases mediate curcumin-induced cell migration in non-tumorigenic colon epithelial cells differing in Apc genotype","volume":"23","author":"Fenton","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1750-2187-8-8","article-title":"EGF regulates tyrosine phosphorylation and membrane-translocation of the scaffold protein Tks5","volume":"8","author":"Fekete","year":"2013","journal-title":"J. Mol. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1267\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:08Z","timestamp":1760027108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031267"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031267","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}